title: Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi.
abstract: Despite improvements in standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone for patients with untreated, diffuse large B-cell lymphoma, up to 40% of these patients relapse. Lenalidomide alone or in combination with rituximab has been shown to be active in relapsed/refractory aggressive lymphomas. In this phase I study we determined the maximum tolerated dose of lenalidomide plus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone in untreated, elderly (median age 68 years) patients with diffuse large B-cell lymphoma. Four lenalidomide doses (5, 10, 15, and 20 mg/day on days 1-14) allocated using the continual reassessment method were planned to be administered for 14 days in combination with each course of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone for a total of six courses. Seven cohorts of patients (n=3 in each cohort) were treated (total n=21) at 10, 20, 15, 15, 15, 10, and 10 mg of lenalidomide. Dose-limiting toxicities occurred in seven patients during the first three courses of treatment. The third dose-level of lenalidomide (15 mg/day) was selected as the maximum tolerated dose, with an estimated probability of dose-limiting toxicities of 0.345 (95% credibility interval 0.164-0.553). Grade 3-4 hematologic adverse events were: neutropenia in 28% of the courses, thrombocytopenia in 9%, and anemia in 3%. Non-hematologic toxicities were moderate: grade 4 increase of creatinine phosphokinase (n=1), grade 3 cardiac (n=2), grade 3 neurological (n=3), and grade 3 gastrointestinal (n=1). In this phase I study, the overall response rate was 90%, with 81% achieving complete remission. This combination regimen appears safe in elderly patients with diffuse large B-cell lymphoma and its efficacy will be assessed in the ongoing phase II trial. This trial was registered at www.clinicaltrials.gov as NCT00907348.
authors.affiliation: uvitolo@cittadellasalute.to.it.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiappella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tucci
authors.forename: Alessia
authors.initials: A
authors.lastname: Castellino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pavone
authors.forename: Ileana
authors.initials: I
authors.lastname: Baldi
authors.forename: Angelo Michele
authors.initials: AM
authors.lastname: Carella
authors.forename: Lorella
authors.initials: L
authors.lastname: Orsucci
authors.forename: Manuela
authors.initials: M
authors.lastname: Zanni
authors.forename: Flavia
authors.initials: F
authors.lastname: Salvi
authors.forename: Anna Marina
authors.initials: AM
authors.lastname: Liberati
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Chiara
authors.initials: C
authors.lastname: Bottelli
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rossini
authors.forename: Sonia
authors.initials: S
authors.lastname: Perticone
authors.forename: Pasqualina
authors.initials: P
authors.lastname: De Masi
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Giovannino
authors.initials: G
authors.lastname: Ciccone
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Umberto
authors.initials: U
authors.lastname: Vitolo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000175:diagnosis / Q000453:epidemiology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D000077269:Lenalidomide; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D013792:Thalidomide; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077269:Lenalidomide; D011241:Prednisone